Elsevier

Neurobiology of Disease

Volume 5, Issue 4, October 1998, Pages 209-227
Neurobiology of Disease

Review
Postherpetic Neuralgia: Irritable Nociceptors and Deafferentation

https://doi.org/10.1006/nbdi.1998.0204Get rights and content

Abstract

Postherpetic neuralgia (PHN) is a common and often devastatingly painful condition. It is also one of the most extensively investigated of the neuropathic pains. Patients with PHN have been studied using quantitative testing of primary afferent function, skin biopsies, and controlled treatment trials. Together with insights drawn from an extensive and growing literature on experimental models of neuropathic pain these patient studies have provided a preliminary glimpse of the pain-generating mechanisms in PHN. It is clear that both peripheral and central pathophysiological mechanisms contribute to PHN pain. Some PHN patients have abnormal sensitization of unmyelinated cutaneous nociceptors (irritable nociceptors). Such patients characteristically have minimal sensory loss. Other patients have pain associated with small fiber deafferentation. In such patients pain and temperature sensation are profoundly impaired but light moving mechanical stimuli can often produce severe pain (allodynia). In these patients, allodynia may be due to the formation of new connections between nonnociceptive large diameter primary afferents and central pain transmission neurons. Other deafferentation patients have severe spontaneous pain without hyperalgesia or allodynia and presumably have lost both large and small diameter fibers. In this group the pain is likely due to increased spontaneous activity in deafferented central neurons and/or reorganization of central connections. These three types of mechanism may coexist in individual patients and each offers the possibility for developing new therapeutic interventions.

References (179)

  • C. Chabal et al.

    Pain responses to perineuromal injection of normal saline, gallamine, and lidocaine in humans

    Pain

    (1989)
  • C. Chabal et al.

    The effect of intravenous lidocaine, tocainide, and mexiletine on spontaneously active fibers originating in rat sciatic neuromas

    Pain

    (1989)
  • L.F. Chapman

    Mechanisms of the flare reaction in human skin

    J. Invest. Dermatol.

    (1977)
  • B. Choi et al.

    Effect of adrenergic receptor activation on post-herpetic neuralgia pain and sensory disturbances

    Pain

    (1997)
  • K. Chung et al.

    Sprouting sympathetic fibers form synaptic varicosities in the dorsal root ganglion of the rat with neuropathic injury

    Brain Res.

    (1997)
  • S.N. Davies et al.

    Evidence for involvement ofN

    Brain Res.

    (1987)
  • G. De Benedittis et al.

    A new topical treatment for acute herpetic neuralgia and post-herpetic neuralgia: the aspirin/diethyl ether mixture. An open-label study plus a double-blind controlled clinical trial

    Pain

    (1992)
  • G. De Benedittis et al.

    Topical aspirin/diethyl ether mixture versus indomethacin and diclofenac/diethyl ether mixtures for acute herpetic neuralgia and postherpetic neuralgia: a double-blind crossover placebo-controlled study

    Pain

    (1996)
  • M. Devor et al.

    Activation of myelinated afferents ending in a neuroma by stimulation of the sympathetic supply in the rat

    Neurosci. Lett.

    (1981)
  • M. Devor et al.

    Systemic lidocaine silences ectopic neuroma and DRG discharge without blocking nerve conduction

    Pain

    (1992)
  • A.H. Dickenson et al.

    The pharmacology of excitatory and inhibitory amino acid-mediated events in the transmission and modulation of pain in the spinal cord

    Gen. Pharmacol.

    (1997)
  • P.M. Dougherty et al.

    Infusion of substance P or neurokinin A by microdialysis alters responses of primate spinothalamic tract neurons to cutaneous stimuli and to iontophoretically released excitatory amino acids

    Pain

    (1995)
  • P.M. Dougherty et al.

    Combined application of excitatory amino acids and substance P produces long-lasting changes in responses of primate spinothalamic tract neurons

    Brain Res. Rev.

    (1993)
  • P.D. Drummond

    Noradrenaline increases hyperalgesia to heat in skin sensitized by capsaicin

    Pain

    (1995)
  • P.K. Eide et al.

    Relief of post-herpetic neuralgia with theNd

    Pain

    (1994)
  • M. Fitzgerald

    Capsaicin and sensory neurones—A review

    Pain

    (1983)
  • R.H. Gracely et al.

    Painful neuropathy: Altered central processing maintained dynamically by peripheral input [see comments]

    Pain

    (1992)
  • H.J. Habler et al.

    Activation of unmyelinated afferents in chronically lesioned nerves by adrenaline and excitation of sympathetic efferents in the cat

    Neurosci. Lett.

    (1987)
  • J.C. Hsieh et al.

    Central representation of chronic ongoing neuropathic pain studied by positron emission tomography

    Pain

    (1995)
  • S.J. Hu et al.

    Sympathetic facilitation of sustained discharges of polymodal nociceptors

    Pain

    (1989)
  • S.P. Hunt et al.

    An immunohistochemical study of neuronal populations containing neuropeptides or γ-aminobutyrate within the superficial layers of the rat dorsal horn

    Neuroscience

    (1981)
  • M.J. Iadarola et al.

    Unilateral decrease in thalamic activity observed with positron emission tomography in patients with chronic neuropathic pain

    Pain

    (1995)
  • W. Janig et al.

    Interactions of sympathetic and primary afferent neurons following nerve injury and tissue trauma

    Prog. Brain Res.

    (1996)
  • K.C. Kajander et al.

    Spontaneous discharge originates in the dorsal root ganglion at the onset of a painful peripheral neuropathy in the rat

    Neurosci. Lett.

    (1992)
  • S.H. Kim et al.

    Sympathectomy alleviates mechanical allodynia in an experimental animal model for neuropathy in the rat

    Neurosci. Lett.

    (1991)
  • R.B. King

    Concerning the management of pain associated with herpes zoster and of postherpetic neuralgia

    Pain

    (1988)
  • E. Kinnman et al.

    Peripheral α-adrenoreceptors are involved in the development of capsaicin induced ongoing and stimulus evoked pain in humans

    Pain

    (1997)
  • M. Koltzenburg et al.

    Dynamic and static components of mechanical hyperalgesia in human hairy skin

    Pain

    (1992)
  • J.M. Laird et al.

    Dorsal root potentials and afferent input to the spinal cord in rats with an experimental peripheral neuropathy

    Brain Res.

    (1992)
  • B. Lynn

    Capsaicin: actions on nociceptive C-fibres and therapeutic potential

    Pain

    (1990)
  • A.R. Abadir et al.

    Postherpetic neuralgia: response to topical clonidine

    Proc. West. Pharmacol. Soc.

    (1996)
  • A.J. Aguayo et al.

    Pathology and pathophysiology of unmyelinated nerve fibers

    Peripheral Neuropathy

    (1975)
  • E. Bahns et al.

    Discharge properties of mechanosensitive afferents supplying the retroperitoneal space

    Pflugers Arch.

    (1986)
  • R. Baron

    Pathophysiological mechanisms in postherpetic neuralgia

    Pain Clin.

    (1996)
  • R. Baron et al.

    Postherpetic neuralgia. Are C-nociceptors involved in signalling and maintenance of tactile allodynia

    Brain

    (1993)
  • R. Baron et al.

    Mechanical allodynia in postherpetic neuralgia: Evidence for central mechanisms depending on nociceptive C-fiber degeneration

    Neurology

    (1995)
  • M. Belenky et al.

    Association of postganglionic sympathetic neurons with primary afferents in sympathetic-sensory co-cultures

    J. Neurocytol.

    (1997)
  • G.J. Bennett

    Animal models of neuropathic pain

  • G.J. Bennett

    Neuropathic pain

  • G.M. Bove et al.

    Unmyelinated nociceptors of rat paraspinal tissues

    J. Neurophysiol.

    (1995)
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    P. J. DyckP. K. ThomasE. H. Lambert

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